Morpholine → 4-(3-Nitro-5-trifluoromethyl-benzoyl)-morpholine

HRID 631454Notes

Reaction equation

HRID 631454 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([OH:9])=O)([O-:3])=[O:2].OC1C2N=NNC=2C=CC=1.CCN=C=NCCCN(C)C.[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>CN(C=O)C>[N:38]1([C:7]([C:6]2[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[O:9])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6166023-Nitro-5-(trifluoromethyl)benzoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 219549894-(3-Nitro-5-trifluoromethyl-benzoyl)-morpholineYield 27.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a round bottomed flask, 3-nitro-5-trifluoromethylbenzoic acid (5.0 g, 21.3 mmoles) was dissolved in 40 mL of dry DMF, to this solution was added hydoxybenzotriazole (5.8 g, 42.5 mmoles) and EDCI (8.2 g, 42.5 mmoles) and the solution stirred for 1 hour at room temperature. At the end of this time morpholine (2.2 g. 25.5 mmoles) was added and the reaction stirred overnight. The solution was then concentrated to dryness, and partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined extracts dried with magnesium sulfate, filtered and concentrated. Chromatography with silica gel and eluting with a ethyl acetate/hexane gradient of 0-35% over 80 minutes gave morpholin-4-yl-(3-nitro-5-trifluoromethyl-phenyl)-methanone (1.8 g). 1H NMR (300 MHz, DMSO-d6) δ 8.6 (d, 2H), 8.3 (s, 1H), 3.8-3.6 (bm, 4H), 3.56 (b, 2H), 3.33 (bs, 2H).

Workup

  1. stirringthe reaction stirred overnight
  2. concentrationThe solution was then concentrated to dryness
  3. custompartitioned between water and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined extracts dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washChromatography with silica gel and eluting with a ethyl acetate/hexane gradient of 0-35% over 80 minutes

Sources & evidence

ORD record
ord-182624b0b0a9474fa18c534ef52feeed
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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